The mechanism responsible for idiotype suppression will be investigated at the cellular as well as the molecular level using an in vitro culture system producing anti-phosphorylcholine (PC) antibodies. Spleen cells from athymic (nude) mice, as well as their thymus-bearing littermates, when treated as neonates with anti-idiotypic sera specifically inhibit the formation of anti-PC antibodies by normal lymphocytes. These data suggest the induction of non-T as well as T suppressor cells following treatment with anti-idiotype antibodies. These suppressor cells will be compared with respect to their cell type and their expression of recognition sites for target cells using various serological reagents. The possible cell-cell interactions between the idiotype-specific and antigen-specific suppressor cells will also be examined to further clarify their regulatory role in antibody production. Moreover, using in vitro methods, the relationship between the suppressor cells and the process of antigen-commitment of B lymphocytes will be determined by correlating the expression of B cell receptors for antigen (i.e., IgM and/or IgD) and the susceptibility of these B cells to idiotype suppression. Finally, the mechanisms involved in the generation of idiotype-specific suppressor cells in vitro will be investigated with an emphasis on the requirements for induction and cell types produced. These studies will provide useful information regarding the mechanisms of tolerance, and a basis for clinical applications using specific suppressor cells generated similarly in vitro.